PremEeze Agnus Castus Capsules THR 33336/0009 UKPAR · The active ingredient in PremEeze Agnus...

MHRA PAR; PREMEEZE AGNUS CASTUS CAPSULES, THR 33336/0009

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PremEeze Agnus Castus Capsules

THR 33336/0009

UKPAR

TABLE OF CONTENTS

Lay summary

Page 2

Scientific discussion

Page 3

Steps taken for assessment

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Summary of Product Characteristics

Page 13

Product Information Leaflet

Page 14

Labelling Page 15


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PREMEEZE AGNUS CASTUS CAPSULES

THR 33336/0009

LAY SUMMARY

The Medicines and Healthcare products Regulatory Agency (MHRA) granted Natures Aid Ltd a Traditional Herbal Registration Certificate for the traditional herbal medicinal product PremEeze Agnus Castus Capsules (Traditional Herbal Registration number: THR 33336/0009) on 19 August 2014. PremEeze Agnus Castus Capsules are available without prescription and can be bought from pharmacies and other outlets. The active ingredient in PremEeze Agnus Castus Capsules comes from the fruit of the Agnus castus plant, which is also known as Vitex agnus castus L. PremEeze Agnus Castus Capsules is a traditional herbal medicinal product used to help relieve premenstrual symptoms such as irritability, mood swings, breast tenderness, bloating and menstrual cramps, based on traditional use only. This registration is based exclusively upon the longstanding use of Agnus castus fruit as a traditional herbal medicine and not upon data generated from clinical trials. There is no requirement under the Traditional Herbal Registration Scheme to prove scientifically that a product works. No new or unexpected safety concerns arose from this application and it was, therefore, decided that a Traditional Herbal Registration Certificate could be granted.


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THR 33336/0009

SCIENTIFIC DISCUSSION

TABLE OF CONTENTS

Introduction

Page 4

Pharmaceutical assessment

Page 5

Non-clinical assessment

Page 8

Clinical assessment

Page 9

Overall conclusions and risk assessment Page 11


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INTRODUCTION

The MHRA granted a Traditional Herbal Registration Certificate for the traditional herbal medicinal product PremEeze Agnus Castus Capsules to Natures Aid Ltd on 19 August 2014. This product is on the general sales list (GSL). This application was submitted according to Article 16.c of Directive 2001/83 EC, as amended, as part of the Traditional Herbal Medicines Registration Scheme. PremEeze Agnus Castus Capsules is a traditional herbal medicinal product used to help relieve premenstrual symptoms such as irritability, mood swings, breast tenderness, bloating and menstrual cramps, based on traditional use only. The data supplied by the applicant demonstrate 30 years of traditional use of Agnus castus fruit in the European Union. A satisfactory review of the available safety data on Agnus castus fruit has also been provided, together with an Expert Safety Report supporting the proposed product.


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PHARMACEUTICAL ASSESSMENT

HERBAL SUBSTANCE: AGNUS CASTUS FRUIT

Scientific name of the plant: Vitex agnus castus L. Plant family: Verbenaceae Manufacture of Herbal Substance The herbal substance is collected manually from the wild in Albania. Collection takes place in September, when the fruit is ripe. Following collection the fruit is cleaned through steam cleaning. The supplier of the Agnus castus fruit has provided confirmation that the herbal substance is produced in accordance with the principles of Good Agricultural and Collection Practice (GACP) (EMEA/HMPC/246816/20050). Control of Herbal Substance The herbal substance is controlled in line with the Ph Eur monograph for Agnus castus fruit, which is acceptable. Container Closure System No details of the container closure system have been provided and none are needed due to the short time between collection and processing. Stability of Herbal Substance No stability data have been provided and none are needed due to the short time between collection and processing. HERBAL PREPARATION: POWDERED AGNUS CASTUS FRUIT Manufacture of Herbal Preparation A satisfactory description of the manufacturing process of the herbal preparation and flow diagram has been provided.

Control of Herbal Preparation A satisfactory specification in line with the Ph Eur monograph for Agnus castus fruit

has been provided and is satisfactory.

Certificates of Analysis have been provided for batches of the herbal preparation, demonstrating satisfactory compliance with the proposed specifications.

Container Closure System Satisfactory details of the container closure system are provided and confirmation has been given that all components of the container closure system comply with current legislation relating to plastic materials and articles intended to come into contact with foodstuffs.


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Stability of Herbal Preparation No stability data are provided for the herbal preparation, which is acceptable as the powdered Agnus castus fruit will be tested immediately before manufacture of the herbal product. HERBAL PRODUCT: PREMEEZE AGNUS CASTUS CAPSULES Description and Composition of Herbal Product PremEeze Agnus Castus Capsules are clear, size 0, hard capsules with a brown powder fill. Each capsule contains 400mg of Agnus castus fruit enclosed in a hypromellose capsule shell. The compatibility of the herbal preparation with the excipient is demonstrated by the stability testing results. The hypromellose is controlled in line with an appropriate specification and representative Certificates of Analysis are provided to demonstrate full compliance.

Manufacture of Herbal Product A flow diagram outlining the various stages of the manufacturing process and the in-process controls is provided. In-process controls are appropriate considering the nature of the product and the method of manufacture. Process validation has been carried out on product batches and the results are satisfactory. Control of Herbal Product The finished product specification is in line with the Ph Eur monograph for Agnus castus fruit and is satisfactory. Batch data have been provided and comply with the release specification. Container Closure System The capsules are stored in Ph Eur type III glass bottles with a polypropylene screw cap incorporating an induction heat seal liner. The bottles are packaged in a printed outer carton containing the Patient Information Leaflet. Pack sizes of 30, 60, 90 and 120 hard capsules have been approved although not all pack sizes may be marketed. Suitable specifications have been provided by the packaging suppliers and it has been confirmed that all primary packaging materials comply with current legislation relating to plastic materials and articles intended to come into contact with foodstuffs. Stability of Herbal Product Finished product stability studies have been conducted in accordance with current guidelines. Based on the results, a product shelf-life of 12 months is appropriate when the storage precautions ‘Store below 25°C’ and ‘Store in the original container’ are applied. Pharmaceutical Expert The Quality Overall Summary has been written by a chemist with suitable experience.


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Product Literature All product literature is satisfactory. A user consultation with target patient groups on the package information leaflet (PIL) has been performed on the basis of a bridging report making reference to EchinEeze Echinacea Tablets (THR 33336/0002) and UCalm St John’s Wort Tablets (THR 33336/0003). The bridging report submitted by the applicant has been found acceptable.

CONCLUSION

There are no objections to granting of a Traditional Herbal Registration from a quality point of view.


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NON-CLINICAL ASSESSMENT

NON-CLINICAL OVERVIEW The applicant has submitted a literature review with this application. An Expert Safety Report was provided, which included reviews of some non-clinical data. The Expert Safety Report was written by a suitably qualified professional. Due to a shortage of published data on Agnus castus fruit, it is not possible to assess if the safety package for the phytochemical constituents of this active ingredient is acceptable to the standards of today’s GLP and safety testing requirements. However, the information supplied demonstrating traditional use is acceptable and thus the lack of provision of a complete standard safety package is acceptable and in compliance with guideline EMEA/HMPC/32116/05. In view of the absence of results of genotoxicity testing, the applicant has provided assurance that results will be provided before the renewal of the registration. The Committee on Herbal Medicinal Products (HMPC) Community Monograph and assessment report for Agnus castus fruit adequately cover any non-clinical safety issues. The overview submitted in support of this application is satisfactory. SUMMARY OF PRODUCT CHARACTERISTICS (SmPC) The SmPC for this product is satisfactory from a non-clinical point of view. ENVIRONMENTAL RISK ASSESSMENT An environmental risk assessment is not required for herbal medicinal products according to guidance CPMP/SWP/4447/00. CONCLUSION There are no objections to granting of a Traditional Herbal Registration from a non-clinical point of view.


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CLINICAL ASSESSMENT

INDICATION The applicant has proposed the following indication: “A traditional herbal medicinal product used to help relieve premenstrual symptoms such as: irritability; mood swings; breast tenderness; bloating and menstrual cramps, based on traditional use only” This indication is acceptable. POSOLOGY AND METHOD OF ADMINISTRATION The applicant has submitted the following: “For oral use only. For women experiencing premenstrual symptoms.

Take 1 capsule 2 times a day (morning and night) swallowed with water.

As treatment effects may not be apparent immediately, the product may need to be taken for up to three months continuously. Maximum daily dose: 2 capsules. If symptoms persist, worsen, or do not improve after 3 months use, a doctor or qualified healthcare practitioner should be consulted.

Women suffering from a pituitary disorder should not take this product (see section 4.3). The use in children and adolescents under 18 years of age is not recommended (see section 4.4 ‘Special warnings and precautions for use’).” This is acceptable. EFFICACY No clinical efficacy data are required for registration of Traditional Herbal Medicinal Products. EVIDENCE OF TRADITIONAL USE Article 16 c 1 (c) requires the applicant to provide bibliographic or expert evidence showing that the medicinal product in question, or a corresponding product, has been in medicinal use throughout a period of at least 30 years, including at least 15 years within the European Community. The herbal preparation in the product under assessment is covered by the HMPC Community Monograph and the HMPC, in drafting the monograph, have accepted the traditional use of Agnus castus fruit. The proposed dosage is within the range recommended by the HMPC Monograph and is acceptable.

The requirements of the Directive are, therefore, considered to be met.


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SAFETY REVIEW Article 16 c 1 (d) requires the applicant to provide a bibliographic review of the safety data together with an Expert Safety Report. The HMPC assessment report for Agnus castus fruit covers the bibliographic data available and the safety of Agnus castus fruit has been demonstrated. The SmPC is in line with the HMPC Monograph. PRODUCT LITERATURE The SmPC, PIL and labelling for this product are medically satisfactory. CONCLUSION There are no objections to granting of a Traditional Herbal Registration from a clinical point of view.


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OVERALL CONCLUSION AND RISK ASSESSMENT

QUALITY The quality data submitted with this application are satisfactory. NON-CLINICAL No new non-clinical data were submitted with this application. However, the published HMPC assessment report and Community Monograph for Agnus castus fruit adopted by the HMPC adequately cover the non-clinical safety issues associated with Agnus castus fruit. EFFICACY AND SAFETY No clinical efficacy data are required for registration of Traditional Herbal Medicinal Products. The published HMPC assessment report and Community Monograph for Agnus castus fruit adopted by the HMPC adequately cover the evidence for traditional use of the herbal preparation in the product under assessment for at least 30 years and the clinical safety issues associated with Agnus castus fruit. The SmPC, PIL and labelling are satisfactory. BENEFIT-RISK ASSESSMENT The quality of the product is acceptable and no new non-clinical or clinical safety concerns have been identified. The risk: benefit balance is acceptable and a Traditional Herbal Registration may be granted.


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THR 33336/0009

STEPS TAKEN FOR ASSESSMENT

1 The MHRA received the Traditional Herbal Registration application on 9 December 2013

2 Following standard checks and communication with the applicant the MHRA considered the application valid on 6 February 2014

3 Following assessment of the application the MHRA requested further information relating to the clinical dossier on 16 April 2014 and the quality dossier on 8 May 2014

4 The applicant responded to the MHRA’s requests, providing further information on the quality dossier on 20 June 2014 and the clinical dossier on 7 August 2014

5 A THR was granted on 19 August 2014


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SUMMARY OF PRODUCT CHARACTERISTICS

The SmPCs for products granted Traditional Herbal Registrations are available on the MHRA website.


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PRODUCT INFORMATION LEAFLET

The PILs for products granted Traditional Herbal Registrations are available on the MHRA website.


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LABELLING


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Label:


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Carton:


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